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Presents hormonal therapy; L represents lung; Li represents Liver ; B represents bone; Bold and italic represent values in patients with low PSA and high BMI1 levels. doi:10.1371/journal.pone.0052993.tDiscussionA prognostic biomarker provides evidence about a patient’s eventual outcomes from a disease independent of a given therapy, whereas a predictive-biomarker estimates the likelihood of response/benefit to a specific therapy in a specific context [22]. PSA still remains the marker of Argipressin web choice for CaP diagnosis, prognosis, and active surveillance. However, PSA has several limitations [23?6]. For example, sipuleucel-T is known to improve survival without having an impact on early PSA levels [27]. PSA progression during CRPC therapy is reported to be prognostic for overall survival but likewise is not a surrogate for overall survival [22]. Some CaP types such as neuroendocrine tumors, produce little if any PSA and decreased 79983-71-4 secretion of PSA in patients suffering from ductal CaP has also been reported [23,25]. In these cases, PSA alterations do not correlate well with clinical benefit [23,25]. There is an unmet need to identify a robust and reliable biomarker which can detect disease progression in patients in whom PSA is not a reliable indicator. Thus, the development of biomarker(s) that can correlate with disease stage along the course of tumor progression is important for intervention and treatment of disease, especially chemoresistant CaP. In the current study, we provide evidence that BMI1 secretory protein has high potential to be developed as a reliable serumbiomarker for human CaP. We provide compelling evidence that BMI1 protein is (i) secreted by tumor cells in greater amounts proportionate to tumor stage and grade, (ii) detectable in blood of human CaP patients in an order of increasing tumor/Gleason Score grade and, (iii) detectable in some CaP patients which exhibit very low levels. Further, we showed a good correlation (r = 0.58) between secretory-PSA and secretory-BMI1 in the serum of human CaP patients. Thus, expression of PSA, along with the detection of BMI1 in serum and biopsy tissue samples, may offer a new approach for CaP diagnosis, prognosis, and active surveillance. We suggest that serum-BMI1 could bring under surveillance some cases in which PSA levels do not correlated with disease progression. African-American men exhibit the worst prognosis of CaP disease which could be due to several reasons [20,28?9]. It is being suggested that absence of a reliable predictive biomarker for African American CaP is one of the contributory factors for thefailure of prognosis in African-American CaP patients. Clinical studies suggested significant differences and in the levels of PSA of between Caucasian and African-American CaP patients [20]. PSA is androgen-dependent and its expression is regulated by androgen receptor [30]. The difference in androgen concentrations between African-American and Caucasian is considered as important factor for the racial disparities in CaP prognosis [20]. It has been reported that androgen receptor expression is 81 higher in African-American CaP patients that in Caucasian and high androgen receptor stimulation has been considered as one of the reasons for CaP development at a younger age with rapid progress in African-American men [29]. Changes in PSA may be informative in patients treat with anti-androgen therapy. However, changes in serum-PSA do not always predict the action of therapy or th.Presents hormonal therapy; L represents lung; Li represents Liver ; B represents bone; Bold and italic represent values in patients with low PSA and high BMI1 levels. doi:10.1371/journal.pone.0052993.tDiscussionA prognostic biomarker provides evidence about a patient’s eventual outcomes from a disease independent of a given therapy, whereas a predictive-biomarker estimates the likelihood of response/benefit to a specific therapy in a specific context [22]. PSA still remains the marker of choice for CaP diagnosis, prognosis, and active surveillance. However, PSA has several limitations [23?6]. For example, sipuleucel-T is known to improve survival without having an impact on early PSA levels [27]. PSA progression during CRPC therapy is reported to be prognostic for overall survival but likewise is not a surrogate for overall survival [22]. Some CaP types such as neuroendocrine tumors, produce little if any PSA and decreased secretion of PSA in patients suffering from ductal CaP has also been reported [23,25]. In these cases, PSA alterations do not correlate well with clinical benefit [23,25]. There is an unmet need to identify a robust and reliable biomarker which can detect disease progression in patients in whom PSA is not a reliable indicator. Thus, the development of biomarker(s) that can correlate with disease stage along the course of tumor progression is important for intervention and treatment of disease, especially chemoresistant CaP. In the current study, we provide evidence that BMI1 secretory protein has high potential to be developed as a reliable serumbiomarker for human CaP. We provide compelling evidence that BMI1 protein is (i) secreted by tumor cells in greater amounts proportionate to tumor stage and grade, (ii) detectable in blood of human CaP patients in an order of increasing tumor/Gleason Score grade and, (iii) detectable in some CaP patients which exhibit very low levels. Further, we showed a good correlation (r = 0.58) between secretory-PSA and secretory-BMI1 in the serum of human CaP patients. Thus, expression of PSA, along with the detection of BMI1 in serum and biopsy tissue samples, may offer a new approach for CaP diagnosis, prognosis, and active surveillance. We suggest that serum-BMI1 could bring under surveillance some cases in which PSA levels do not correlated with disease progression. African-American men exhibit the worst prognosis of CaP disease which could be due to several reasons [20,28?9]. It is being suggested that absence of a reliable predictive biomarker for African American CaP is one of the contributory factors for thefailure of prognosis in African-American CaP patients. Clinical studies suggested significant differences and in the levels of PSA of between Caucasian and African-American CaP patients [20]. PSA is androgen-dependent and its expression is regulated by androgen receptor [30]. The difference in androgen concentrations between African-American and Caucasian is considered as important factor for the racial disparities in CaP prognosis [20]. It has been reported that androgen receptor expression is 81 higher in African-American CaP patients that in Caucasian and high androgen receptor stimulation has been considered as one of the reasons for CaP development at a younger age with rapid progress in African-American men [29]. Changes in PSA may be informative in patients treat with anti-androgen therapy. However, changes in serum-PSA do not always predict the action of therapy or th.